A negative Vizamyl scan
indicates sparse to no neuritic plaques and is inconsistent with a
neuropathological diagnosis of AD at the time of image acquisition; a negative
scan result reduces the likelihood that a patient's cognitive impairment is due
to AD. A positive Vizamyl scan indicates moderate to frequent amyloid neuritic
plaques; neuropathological examination has shown this amount of amyloid
neuritic plaque is present in patients with AD, but may also be present in
patients with other types of neurologic conditions as well as in older people
with normal cognition. Vizamyl is an adjunct to other diagnostic evaluations.

Limitations of Use

A positive Vizamyl scan does not establish a diagnosis of
AD or other cognitive disorder.

DOSAGE AND ADMINISTRATION

Radiation Safety -Drug Handling

Vizamyl is a radioactive drug and should be handled with
safety measures to minimize radiation exposure during administration [see WARNINGS
AND PRECAUTIONS]. Use waterproof gloves and effective shielding, including
lead-glass syringe shields when handling and administering Vizamyl. To minimize
radiation dose to the bladder, encourage patients to hydrate before and after
Vizamyl administration in order to permit frequent voiding. Encourage patients
to void before and after imaging with Vizamyl and frequently thereafter for 24
hours following Vizamyl administration.

Radiopharmaceuticals, including Vizamyl, should be used
by or under the control of physicians who are qualified by specific training
and experienced in the safe use and handling of radioactive materials, and
whose experience and training have been approved by the appropriate
governmental agency authorized to license the use of radiopharmaceuticals.

Recommended Dosing And Administration Procedures

The recommended dose for Vizamyl is 185 megabecquerels
(MBq) [5 millicuries (mCi)] in a maximum dose volume of 10 mL, administered as
a single intravenous bolus within 40 seconds. The maximum mass dose is 20
micrograms. Follow the injection with an intravenous flush of 5 to 15 mL of
0.9% sterile sodium chloride injection.

Use aseptic technique and radiation shielding to withdraw
and administer Vizamyl solution.

Calculate the necessary volume to administer based on
calibration time and dose using a suitably calibrated instrument.

Visually inspect Vizamyl for particulate matter and
discoloration prior to administration. Do not administer Vizamyl if it contains
particulate matter or is discolored [see DESCRIPTION].

Do not dilute Vizamyl.

Dispose of unused product in a safe manner in compliance
with applicable regulations [see Storage and Handling].

Imaging Acquisition Guidelines

A 20-minute PET image should be acquired starting 90
minutes after Vizamyl injection, using a PET scanner in 3-D mode with appropriate
data corrections. Position the patient supine with the brain (including the
cerebellum) within a single field of view. The patient's head should be tilted
so that the anterior commissure-posterior commissure (AC-PC) plane is at right
angles to the bore-axis of the PET scanner, with the head positioned in a
suitable head support. Reducing head movement with tape or other flexible head
restraints may be employed.

Iterative or filtered back-projection reconstruction is
recommended with a slice thickness of 2 to 4 mm, matrix size of 128 x 128 with
pixel sizes of approximately 2 mm. Where a post-smoothing filter is applied, a
full width half maximum (FWHM) of not more than 5 mm is recommended; filter
FWHM should be chosen to optimize the signal-to-noise ratio while preserving
the sharpness of the reconstructed image.

Image Orientation And Display

Image Orientation

Orient axial and coronal images to show symmetry of brain
structures, with equal heights of structures bilaterally. Orient sagittal
images so that the head and neck are neither flexed nor extended; the anterior
and posterior aspects of the corpus callosum should be parallel to the AC-PC
line as shown in Figure 2.

Image Display

Display images with all planes (axial, sagittal and
coronal planes) linked by crosshairs.

Select a color scale that provides a progression of low
through high intensity (e.g., rainbow or Sokoloff). The selected color scale
should (1) provide colors that allow the reader to discriminate intensity
levels above and below the intensity level of the pons, (2) provide a color for
regions with little or no amyloid binding such as the cerebellarcortex, and
(3) provide a range of at least five distinct colors above 50 to 60% of the
peak intensity.

Display the reference scale. Adjust the color scale to
set the pons to approximately 90% maximum intensity. The cerebellar cortex
should represent approximately 20-30% of peak intensity on both negative and
positive Vizamyl scans.

Briefly display axial brain slices from bottom to top and
look for signs of atrophy.

Systematically review the following brain regions
(recommended plane) for flutemetamol F18 uptake as described in Image
Interpretation below:

Image Interpretation

Vizamyl images should be interpreted only by readers who
successfully complete the electronic training program provided by the
manufacturer [see WARNINGS AND PRECAUTIONS]. The objective of Vizamyl
image interpretation is to provide an estimate of the brain β-amyloid
neuritic plaque density, not to make a clinical diagnosis. Image interpretation
is performed independently of a patient's clinical features and relies upon
recognition of image features in certain brain regions.

Image interpretation is based upon the distribution of
radioactive signal within the brain; clinical information is not a component of
image assessment [see WARNINGS AND PRECAUTIONS]. Images are designated
as positive or negative either by comparing radioactivity in cortical grey
matter with activity in adjacentwhite matter, or based on the intensity in the
five regions mentioned above. Signal uptake in the cerebellum does not
contribute to scan interpretation (for example, a positive scan may show
retained cerebellar grey-white contrast even when the cortical grey-white
contrast is lost). Images should be viewed with the minimum image intensity set
to zero and the maximum set such that the signal level in the easily
identifiable pons is at 90% of maximum.

Negative scansshow more radioactivity in
white matter than in grey matter, creating clear grey-white matter contrast.
Specifically, a negative scan would have the following characteristics:

striatum: approximately 50% of peak intensity or lower in
the region between the higher intensities of the thalamus and frontal white
matter (striatal “gap”)

Positive scans show at least one cortical region
with reduction or loss of the normally distinct grey-white matter contrast.
These scans have one or more regions with increased cortical grey matter signal
(above 50-60% peak intensity) and/or reduced (or absent) grey-white matter
contrast (white matter sulcal pattern is less distinct). A positive scan may
have one or more regions in which grey matter radioactivity is as intense or
exceeds the intensity in adjacent white matter.

Specifically, a positive scan would have the following
characteristics:

frontal, lateral temporal, or inferolateral parietal
lobes: high intensity seen to the periphery of the brain, with sharp reduction
of intensity at the brain margin; sulci not distinct due to fill-in by high
intensity grey matter resulting in a convex surface at the edge of the brain,

or

posterior cingulate and precuneus: grey matter uptake
above 50-60% of peak intensity; high grey matter intensity that closes the gap
between the two hemispheres on coronal view,

If any one of the brain regions systematically reviewed
for flutemetamol F18 uptake (see Image Orientation and Display above) is
positive in either hemisphere, then the scan is considered positive. Otherwise,
the scan is considered negative.

Among patients with clinically important β-amyloid
neuritic plaques in the brain, the temporal lobes, parietal lobes, and striatum
may not be as affected compared to other brain regions. Therefore, in some
images, flutemetamol F18 signal in these regions may not be as intense as in
the frontal lobes or the posterior cingulate and precuneus regions.

Atrophy may affect the interpretability of scans,
particularly in the frontal, temporal and parietal lobes [see WARNINGS AND
PRECAUTIONS]. For cases in which atrophy is apparent or suspected and there
is uncertainty as to the location of the grey matter on the PET scan, examine
the striatum for flutemetamol F18 signal as it is less affected by atrophy than
other regions of the brain.

If the patient's MRI or CT brain images are available the
interpreter should examine the CT or MRI images to clarify the relationship
between PET flutemetamol F18 uptake and grey matter anatomy.

Other factors that may affect the ability to interpret
Vizamyl images include patient factors such as brain pathology, surgical
changes, post-radiation therapy changes, and implants. Some scans may be
difficult to interpret due to image noise, suboptimal patient positioning, or
over-smoothing of the reconstructed image.

Figure 1: Axial view of negative (left) and positive
(right) Vizamyl scans. The axial slices which cut through the frontal pole
and inferior aspect of the splenium are shown using a rainbow color scale. The
left image shows a white matter sulcal pattern at the frontal (f) and lateral
temporal (lt) regions with a color intensity that tapers to the periphery, as
well as less radioactivity in the striatal region(s). The right image shows
absence of the white matter sulcal pattern with intensity radiating to a sharply
defined convex edge, as well as more radioactivity in the striatum. In both the
frontal and lateral temporal regions, the intensity is higher in the grey
matter regions of the right image compared to those of the left image.

Figure 2: Sagittal view of
negative (left) and positive (right) Vizamyl scans. The sagittal slices are slightly off midline in one
hemisphere and shown using a rainbow color scale. In the posterior cingulate
(pc) region, which is superior and posterior to the corpus callosum (cc), the
left image shows intensity below 50% of peak intensity whereas the right image
shows intensity above 60% of peak intensity. The pons (p) is set to
approximately 90% of the maximum intensity.

Figure 3: Coronal view of
negative (left) and positive (right) Vizamyl scans. The coronal slices are located posterior to the corpus
callosum. The left image shows a white matter sulcal pattern in the inferior
parietal (ip) regions that is not evident in the right image. Relative to the
left image, the right image shows increased intensity in the posterior cinguli
(pc) and increased radial extent of high intensity to the lateral surfaces of
the parietal lobes particularly evident in the inferior parietal regions.

Radiation Dosimetry

The estimated absorbed
radiation doses for adult patients following intravenous injection of Vizamyl
are shown in Table 1. Values were calculated from human biodistribution data
using OLINDA/EXM software and assuming emptying of the urinary bladder at 3.5-hour
intervals.

The adult effective dose
resulting from a 185-MBq (5-mCi) Vizamyl administration is 5.92 mSv. The use of
a CT scan to calculate attenuation correction for reconstruction of Vizamyl
images (as done in PET/CT imaging) will add radiation exposure at the level of
approximately 0.1 mSv effective dose. Diagnostic head CT scans using helical
scanners administer an average of 2.2 ± 1.3 mSv effective dose. The actual
radiation dose is operator and scanner dependent.

HOW SUPPLIED

Dosage Forms And Strengths

Vizamyl injection is available
in a 10-mL or 30-mL multi-dose vial containing a clear, colorless to slightly
yellow solution at a strength of 150 MBq/mL [4.05 mCi/mL] of flutemetamol F 18
at reference date and time.

Storage And Handling

Vizamyl is supplied in a 10-mL
or a 30-mL multi-dose glass vial with 1-10 mL and 1-30 mL fill volume
respectively. Each vial is enclosed in an appropriate radiation shield. The
total concentration is 150 MBq/mL (4.05 mCi/mL) of flutemetamol F 18 at
reference date and time.